α1－アンチトリプシン欠乏症

INTRODUCTION AND OBJECTIVES: Alpha-1 antitrypsin deficiency is associated with lung and liver disease, but its role in lung carcinogenesis remains unclear. This study aimed to compare the clinical, functional, and molecular characteristics of lung cancer according to alpha-1 antitrypsin (AAT) genotype and, additionally, to explore differences by sex and the possible influence of environmental exposures. PATIENTS AND METHODS: We conducted a cross-sectional, single-centre study including 407 patients with incident lung cancer diagnosed between 2020 and 2023. Clinical, functional, radiological, molecular, and environmental variables were collected. Comparisons were performed between carriers and non-carriers of altered AAT alleles and between women and men. RESULTS: Of the 394 patients with available genotyping, 24.4% carried at least one altered allele. No significant differences were observed by genotype in smoking status, radon exposure, comorbidities, lung function, or histological subtype. Carriers showed significantly lower serum AAT levels and a higher frequency of values < 116 mg/dL (p < 0.001). PD-L1 expression ≥ 50% was more common in carriers (28.1% vs. 19.4%; p = 0.036). In the multivariable analysis, the altered AAT genotype remained independently associated with a higher probability of PD-L1 expression ≥ 50% (aOR = 2.04; 95% CI: 1.09-3.80; p = 0.026). Women had lower cumulative tobacco exposure, lower prevalence of emphysema and COPD, greater biomass exposure, higher frequency of adenocarcinoma, and more EGFR mutations (p < 0.001). CONCLUSIONS: Patients carrying altered AAT alleles did not exhibit a distinctly different clinical profile, although they showed higher PD-L1 expression (≥50%). Furthermore, significant differences were observed between women and men in terms of exposure, histology and molecular alterations.

Inflammatory infiltrates of the subcutis are a particular challenge in routine histopathology as they occur relatively rarely in submitted specimens and often only superficial portions of adipose tissue are captured in biopsies. On the other hand, panniculitides are very heterogeneous in etiology. They can arise as a reaction to physical stimuli, in metabolic disorders, as a drug reaction, in autoimmune diseases or due to pathogens. The correct classification of infiltrate patterns of adipose tissue and knowledge of associated features and diagnostic clues are essential for narrowing down the differential diagnosis. This is illustrated using more common panniculitides (lupus profundus, erythema nodosum, lipodermatosclerosis). In addition, rarer adipose tissue diseases (alpha‑1 antitrypsin deficiency, pancreatic panniculitis, morphea profunda, eosinophilic fasciitis) and vasculitides that should be considered in the differential diagnosis are discussed.

PURPOSE: Alpha-1 Antitrypsin Deficiency (A1ATD) is associated with an increased risk of emphysema and chronic obstructive pulmonary disease (COPD). In view of the high prevalence of chronic respiratory diseases in East Tennessee and limited data on A1AT phenotypes in this area, we determined A1AT allele frequency among patients with COPD, asthma, or asthma-COPD overlap (ACO) in our clinic population. PATIENTS AND METHODS: We conducted an IRB-approved retrospective analysis of patient demographics, medical history, comprehensive pulmonary function tests (PFTs), and serum A1AT levels and phenotypes in a cohort of general pulmonary clinic patients with COPD, asthma, or ACO at the University of Tennessee Medical Center in Knoxville, TN. We employed descriptive and nonparametric statistical methods for data analysis, and an alpha value < 0.05 was considered statistically significant. RESULTS: In this cohort of 177 patients (mean age 63.2 ± 11.9 years), most were white (94.4%), female (59.3%), former or current smokers (79.1%), and homozygous for the normal PiMM A1AT phenotype (78.5%). Heterozygous A1AT phenotypes PiMS, PiMZ, PiSZ, and PiXZ were found in 23.9%, 20%, and 8.3% of patients with COPD, ACO, and asthma, respectively. Compared with PiMM, serum A1AT levels were significantly lower with PiMZ, PiSZ, and PiXZ phenotypes (p < 0.001). PFTs did not differ among A1AT phenotypes. In fact, there was a weak negative correlation between serum A1AT levels and forced vital capacity (r = -0.29; p = 0.01) and diffusion capacity for carbon monoxide (r = -0.27; p = 0.03). CONCLUSION: Among our East Tennessee cohort with COPD, asthma, or ACO, we found a 2- to 6-fold higher prevalence of heterozygous A1AT phenotypes than a national survey of US veterans. Further investigation through larger, prospective, population-based studies is needed to determine the clinical relevance of the higher prevalence of A1AT heterozygotes in this region.